Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
J Cell Biol. 2022 Jul 4;221(7). doi: 10.1083/jcb.202008116. Epub 2022 May 5.
The planar cell polarity pathway regulates cell polarity, adhesion, and rearrangement. Its cytoplasmic core components Prickle (Pk) and Dishevelled (Dvl) often localize as dense puncta at cell membranes to form antagonizing complexes and establish cell asymmetry. In vertebrates, Pk and Dvl have been implicated in actomyosin cortex regulation, but the mechanism of how these proteins control cell mechanics is unclear. Here we demonstrate that in Xenopus prechordal mesoderm cells, diffusely distributed, cytoplasmic Pk1 up-regulates the F-actin content of the cortex. This counteracts cortex down-regulation by Dvl2. Both factors act upstream of casein kinase II to increase or decrease cortical tension. Thus, cortex modulation by Pk1 and Dvl2 is translated into mechanical force and affects cell migration and rearrangement during radial intercalation in the prechordal mesoderm. Pk1 also forms puncta and plaques, which are associated with localized depletion of cortical F-actin, suggesting opposite roles for diffuse and punctate Pk1.
平面细胞极性途径调节细胞极性、黏附和重排。其细胞质核心成分 Prickle (Pk) 和 Dishevelled (Dvl) 通常在细胞膜上定位于密集的点状结构,形成拮抗复合物并建立细胞不对称性。在脊椎动物中,Pk 和 Dvl 已被牵涉到肌动球蛋白皮层的调节,但这些蛋白质如何控制细胞力学的机制尚不清楚。在这里,我们证明在非洲爪蟾前脑脊索中胚层细胞中,弥散分布的细胞质 Pk1 上调皮层的 F-肌动蛋白含量。这抵消了 Dvl2 对皮层的下调作用。这两个因素都作用于酪蛋白激酶 II 的上游,增加或减少皮层张力。因此,Pk1 和 Dvl2 对皮层的调节被转化为机械力,并影响前脑脊索中胚层的径向内插过程中的细胞迁移和重排。Pk1 还形成点状和斑状结构,这些结构与皮层 F-肌动蛋白的局部耗竭有关,这表明弥散和点状 Pk1 具有相反的作用。